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Oncology

2023

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Full-Text Articles in Cell and Developmental Biology

Predicting Stage Progression In Binet Stage A Chronic Lymphocytic Leukemia, Salem H. Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M. Isaac, Andy Kaempf Dec 2023

Predicting Stage Progression In Binet Stage A Chronic Lymphocytic Leukemia, Salem H. Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M. Isaac, Andy Kaempf

Hematology/Oncology and Stem Cell Therapy

Introduction: the variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. Methods: this study involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E). We evaluated the applicability of these prognostic indices in our young, Middle Eastern cohort (median age 59 at diagnosis). Results: during a study period …


Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang Oct 2023

Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA+), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …


Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut Oct 2023

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …


The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle Sep 2023

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …


Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung Aug 2023

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …


A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy Aug 2023

A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy

Electronic Theses and Dissertations

Breast cancer is the second most occurring cancer type and is ranked fifth in terms of mortality. X-ray mammography is the most common methodology of breast imaging and can show radiographic signs of cancer, such as masses and calcifcations. From these mammograms, radiologists can also assess breast density, which is a known cancer risk factor. However, since not all dense tissue is cancer-prone, we hypothesize that dense tissue can be segregated into healthy vs. risky subtypes. We propose that risky dense tissue is associated with tissue microenvironment disorganization, which can be quantified via a computational characterization of the whole breast …


To Compare The Safety And Efficacy Of Intraluminal Brachytherapy Vs Isolated Percutaneous Transhepatic Biliary Drainage For Unresectable Malignant Biliary Obstruction - A Prospective Observational Study, Shikha Sood, John V Alexander, Manish Gupta, Ashish Chauhan Aug 2023

To Compare The Safety And Efficacy Of Intraluminal Brachytherapy Vs Isolated Percutaneous Transhepatic Biliary Drainage For Unresectable Malignant Biliary Obstruction - A Prospective Observational Study, Shikha Sood, John V Alexander, Manish Gupta, Ashish Chauhan

Hematology/Oncology and Stem Cell Therapy

BACKGROUND: Intraluminal therapies like brachytherapy can locally destroy the obstructing tumour and thus increase the duration of catheter/stent patency in patients with unresectable malignant biliary obstruction (MBO). OBJECTIVES: Evaluate the safety and efficacy of percutaneous transhepatic biliary drainage (PTBD) followed by HDR Intraluminal Brachytherapy (ILBT) in the palliative treatment of malignant biliary obstruction. DESIGN: Prospective observational study SETTING: An academic tertiary care hospital in Himachal Pradesh PATIENT AND METHODS: All consenting consecutive patients of MBO from January 2021 to March 2022, who were unfit for alternate treatment modalities were enrolled in our study and underwent percutaneous transhepatic biliary drainage (PTBD) …


Assessing The Efficacy Of Mitoxantrone And Doxorubicin As Frontline Anthracyclines During Induction Therapy Of Newly Diagnosed Acute Promyelocytic Leukemia, José Carlos Jaime-Pérez, Eugenia M. Ramos-Dávila, Jesús D. Meléndez-Flores, Mariana González-Treviño, David Gómez-Almaguer Aug 2023

Assessing The Efficacy Of Mitoxantrone And Doxorubicin As Frontline Anthracyclines During Induction Therapy Of Newly Diagnosed Acute Promyelocytic Leukemia, José Carlos Jaime-Pérez, Eugenia M. Ramos-Dávila, Jesús D. Meléndez-Flores, Mariana González-Treviño, David Gómez-Almaguer

Hematology/Oncology and Stem Cell Therapy

Background: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today’s most curable form of leukemia. However, recommended agents such as arsenic trioxide, idarubicin or daunorubicin are not easily available in low-middle-income countries, in which outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines. Materials: We conducted a retrospective cohort including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25mg/m2) with mitoxantrone or doxorubicin as induction to remission therapy. Groups were compared using the χ2 and Student’s T-tests. Kaplan–Meier analysis was used for survival …


Role Of Anti-Cd38 Monoclonal Antibodies In The Treatment Of Adult Immune Hematological Diseases., Erin Huilin Yang, Ibrahim N. Muhsen, Hadeel Samarkandi, Riad El Fakih, Mahmoud Aljurf, Amr Hanbali Aug 2023

Role Of Anti-Cd38 Monoclonal Antibodies In The Treatment Of Adult Immune Hematological Diseases., Erin Huilin Yang, Ibrahim N. Muhsen, Hadeel Samarkandi, Riad El Fakih, Mahmoud Aljurf, Amr Hanbali

Hematology/Oncology and Stem Cell Therapy

Daratumumab is a first-in-class human anti-CD38 IgG1 monoclonal antibody approved for the treatment of newly diagnosed as well as relapsed refractory multiple myeloma. Preclinical data supported dararumumab ability in depleting autoantibodies producing-plasma cells, B-cells as well as NK cells. Those reports showed promising results on the use of daratumumab in autoimmune disorders refractory to multiple lines of therapies, which encouraged the use of daratumumab in various autoimmune conditions that are refractory to standard therapies. The aim of this review is to summarize the literature reporting experience using anti-CD38 antibodies in hematological autoimmune diseases, focusing on the most common autoimmune hematological …


Invasive Pulmonary Aspergillosis In Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based On The United States National Readmission Database, Amir Khalil, Paramveer Singh, Tanveer Mir, Mohammed Uddin, Ayman O. Soubani Aug 2023

Invasive Pulmonary Aspergillosis In Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based On The United States National Readmission Database, Amir Khalil, Paramveer Singh, Tanveer Mir, Mohammed Uddin, Ayman O. Soubani

Hematology/Oncology and Stem Cell Therapy

Background and Objective: Hematopoietic Stem Cell Transplant (HSCT) is well established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. Our primary objective was to assess whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among patients undergoing HSCT. A secondary objective was to examine potential differences in complications between HSCT with IPA and HSCT without IPA. Materials and Methods: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and …


A Single Centre, Real-World Experience Of Chronic Gvhd Treatment Using Ibrutinib, Imatinib And Ruxolitinib And Its Treatment Outcomes, Swe Mar Linn, Igor Novitzky-Basso, Omar Abduljalil, Ivan Pasic, Wilson Lam, Arjun Law, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Dennis Dong Hwan Kim Aug 2023

A Single Centre, Real-World Experience Of Chronic Gvhd Treatment Using Ibrutinib, Imatinib And Ruxolitinib And Its Treatment Outcomes, Swe Mar Linn, Igor Novitzky-Basso, Omar Abduljalil, Ivan Pasic, Wilson Lam, Arjun Law, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Dennis Dong Hwan Kim

Hematology/Oncology and Stem Cell Therapy

Background: Chronic graft-versus-host-disease (cGVHD) is a common cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT). Tyrosine kinase inhibitors (TKIs), including Ruxolitinib, Imatinib and Ibrutinib, have shown promising efficacy in cGVHD treatment. Method: A total of 43 patients who developed cGVHD and received at least one line of TKI therapy for cGVHD treatment were evaluated retrospectively. Overall response, clinical benefit (CB), corticosteroid dose reduction, failure-free (FFS) and overall survival (OS) were assessed. Result: A total 62 lines of TKI therapy were evaluated, including Ruxolitinib (n=18), Ibrutinib (n=13), and Imatinib (n=31). With a median follow-up duration of 12 …


Is Mixed Chimerism Post Allogeneic Hematopoietic Stem Cell Transplantation In Pediatric Acute Lymphoid Leukemia A Prognostic Factor For Relapse ?, Saadiya Khan, Zainab Alsaif, Khawar Siddiqui, Hawazen Alsaedi, Ali Al-Ahmari, Abdullah Al-Jefri, Ibrahim Ghemlas, Awatif Alanazi, Mouhab Ayas Aug 2023

Is Mixed Chimerism Post Allogeneic Hematopoietic Stem Cell Transplantation In Pediatric Acute Lymphoid Leukemia A Prognostic Factor For Relapse ?, Saadiya Khan, Zainab Alsaif, Khawar Siddiqui, Hawazen Alsaedi, Ali Al-Ahmari, Abdullah Al-Jefri, Ibrahim Ghemlas, Awatif Alanazi, Mouhab Ayas

Hematology/Oncology and Stem Cell Therapy

Hematopoietic Stem Cell Transplantation (HSCT) has been considered curative for children with high-risk acute leukemia (ALL) offering better survival. Short tandem repeat (STR) has been used as a marker of chimerism status after HSCT. The appearance of recipient cells >1% post allogenic stem cell transplant was defined as mixed chimerism (MC). Chimeric studies post HSCT are dynamic. The aim of this study was to study the significance of recipients cells in post-HSCT pediatric ALL patients as a predictor of relapse of their primary disease. Rate of MC was 51.4% (19 out of 37 recipients). It was 48.6% (n=18) during Day+100 …


Side Effects After Use Of Bedside Thaw Method In An Umbilical Cord Blood Stem Cells For Allogeneic Transplantation In A Children Cohort: A Single-Center Experience., Natalia Builes, Laura Niño-Serna, Juan Felipe Combariza Jun 2023

Side Effects After Use Of Bedside Thaw Method In An Umbilical Cord Blood Stem Cells For Allogeneic Transplantation In A Children Cohort: A Single-Center Experience., Natalia Builes, Laura Niño-Serna, Juan Felipe Combariza

Hematology/Oncology and Stem Cell Therapy

Background: Several strategies and procedures have been described for thawing umbilical cord blood (UCB) products. The ideal method for each center depends on the resources, staff training and access to each of them. Method: We retrospectively evaluated the incidence of side effects using the bedside thaw method after unrelated UCB transplantation in 34 children. Patient, donor, graft characteristics and side effects were identified. In addition, we attempt to identify the risk factors that could be associated with side effects. Result: Sixty-eight percent of patients experienced any adverse reaction. All the reactions were mild and transient events. The most frequent side …


Analysis Of Macrophage Migration Inhibitory Factor Genotype In Hemophilia A Patients, Murtadha Ali Hadi, Wijdan Nazar Ibrahim, Meaad Kadhum Hassan Jun 2023

Analysis Of Macrophage Migration Inhibitory Factor Genotype In Hemophilia A Patients, Murtadha Ali Hadi, Wijdan Nazar Ibrahim, Meaad Kadhum Hassan

Hematology/Oncology and Stem Cell Therapy

Background Hemophilia A, an X-linked bleeding disorder, is caused by a complete or partial deficiency in Factor VIII. Multiple factors play a role in the development and progression of bleeding episodes, especially arthropathy, in hemophilia patients. Objectives Detection of macrophage migration inhibitory factor (MIF)-173 G/C polymorphism in people with hemophilia A (PWH) and the possible associations between the type of MIF gene polymorphism and selected disease-related variables. Subjects and Methods This case–control study included 95 male patients aged 2 months to 63 years with hemophilia A and 95 nonhemophiliac subjects matched for age and sex. Allele-specific polymerase chain reaction (AS-PCR) …


Oncotypedx Testing Does Not Benefit Patients With Grade 1, Estrogen And Progesterone Receptor Positive Breast Cancers: A Tailorx Validated Study, Udai S. Sibia, W. Charles Mylander, Tasha Martin, Martin Rosman, Thomas J. Sanders, Young Lee, Lorraine Tafra, Rubie S. Jackson Jun 2023

Oncotypedx Testing Does Not Benefit Patients With Grade 1, Estrogen And Progesterone Receptor Positive Breast Cancers: A Tailorx Validated Study, Udai S. Sibia, W. Charles Mylander, Tasha Martin, Martin Rosman, Thomas J. Sanders, Young Lee, Lorraine Tafra, Rubie S. Jackson

Hematology/Oncology and Stem Cell Therapy

Background & Objectives We previously described a predictive AAMC model that identifies patients (grade 1, hormone positive) who would not benefit from OncotypeDX testing. The purpose of this study was to validate the AAMC model by assessing distant recurrence-free interval (DRFI) and invasive disease-free survival (IDFS) using TAILORx clinical trial data. Materials & Methods We retrospectively analyzed TAILORx trial data and categorized patients based on the AAMC model. AAMC low-risk patients are those with grade 1 and hormone positive tumors. Kaplan-Meier curves examined DRFI and IDFS. Results Of the total 9195 cases, 2246 (24.4%) were identified as AAMC low-risk. Among …


Post Autologous Hematopoietic Cell Transplant Care In The “Home Sweet Home” Setting: A Treatment Paradigm Shift, Mohamed A. Kharfan-Dabaja, Vivek Roy, Hemant Murthy, Deborah Fischer, Razan Mohty, Ashley Greathouse, Alethea Brown, Kathryn Moreno, Emily Godsey, Jennifer M. Higginbotham, Ashley Bartholomew, Alexis Jackson, Ricardo A. Torres-Guzman, Antonio J. Forte, Sikander Ailawadhi, Roxana Dronca, Michael Maniaci Jun 2023

Post Autologous Hematopoietic Cell Transplant Care In The “Home Sweet Home” Setting: A Treatment Paradigm Shift, Mohamed A. Kharfan-Dabaja, Vivek Roy, Hemant Murthy, Deborah Fischer, Razan Mohty, Ashley Greathouse, Alethea Brown, Kathryn Moreno, Emily Godsey, Jennifer M. Higginbotham, Ashley Bartholomew, Alexis Jackson, Ricardo A. Torres-Guzman, Antonio J. Forte, Sikander Ailawadhi, Roxana Dronca, Michael Maniaci

Hematology/Oncology and Stem Cell Therapy

Multiple myeloma (MM) is the second most common hematologic malignancy with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) is a standard treatment for MM even in the era of novel therapies. This is usually done in hospital-based setting, whether in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with vendor-mediated supply chain capable of delivering high-acuity care in the comfort of patient’s own homes. In our program, we leveraged the existing ACH platform to deliver post-HCT care …


Cytogenetically Normal Acute Myeloid Leukaemia At A Single Centre In South Africa, Nicholas Jenkins, Lee-Ann Phillips, Marian Stone, Estelle Verburgh, Jenna Oosthuizen, Karen Shires Jun 2023

Cytogenetically Normal Acute Myeloid Leukaemia At A Single Centre In South Africa, Nicholas Jenkins, Lee-Ann Phillips, Marian Stone, Estelle Verburgh, Jenna Oosthuizen, Karen Shires

Hematology/Oncology and Stem Cell Therapy

Background: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge. The European Leukaemia Net 2017 guidelines attempted to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. Objectives: This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple-mutation testing approach for risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin (NPM1), fms-like tyrosine kinase internal …


Peritoneal And Pleural Drains In Pediatric Hematopoietic Cell Transplant Recipients With Veno-Occlusive Disease Are Safe And Do Not Adversely Impact Clinical Outcomes, Hemalatha G. Rangarajan, Vinita B Pai Pharm, Joseph R. Stanek, Cassandra Rush Pharm, Jeffrey Naples, Misti Drope, Veronika Polishchuk, Rolla Abu Arja, Rajinder Ps Bajwa Jun 2023

Peritoneal And Pleural Drains In Pediatric Hematopoietic Cell Transplant Recipients With Veno-Occlusive Disease Are Safe And Do Not Adversely Impact Clinical Outcomes, Hemalatha G. Rangarajan, Vinita B Pai Pharm, Joseph R. Stanek, Cassandra Rush Pharm, Jeffrey Naples, Misti Drope, Veronika Polishchuk, Rolla Abu Arja, Rajinder Ps Bajwa

Hematology/Oncology and Stem Cell Therapy

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study we compared the clinical outcomes and health resource utilization (HRU) in 32 patients with VOD who had a PD placed (PD+) post HCT with 27 patients who did not (PD-). Nine patients had a CT (7 PD+ and 2 PD-). PD+ patients were more likely than PD- patients to have received myeloablative conditioning (100% vs 85.2%; p=0.04) and have severe or very …


Post-Transplantation Cyclophosphamide Based Graft-Versus-Host-Disease Prophylaxis Compared To Methotrexate-Cyclosporine A In Matched Related Allogeneic Hematopoietic Stem Cell Transplantation, Mohamed Shouman, Osman Mansour, Mosaad M. El Gammal, Raafat Abdel-Fattah, Mohamed A. Samra, Alaa El Haddad, Mohamed Maher, Hossam K. Mahmoud Jun 2023

Post-Transplantation Cyclophosphamide Based Graft-Versus-Host-Disease Prophylaxis Compared To Methotrexate-Cyclosporine A In Matched Related Allogeneic Hematopoietic Stem Cell Transplantation, Mohamed Shouman, Osman Mansour, Mosaad M. El Gammal, Raafat Abdel-Fattah, Mohamed A. Samra, Alaa El Haddad, Mohamed Maher, Hossam K. Mahmoud

Hematology/Oncology and Stem Cell Therapy

Background: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce.

Objective: The study aimed to evaluate the rates of GVHD and survival outcomes in patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA matched related donors (MRD) receiving PTCy based GVHD prophylaxis and to compare it with the outcomes of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis.

Patients and Methods: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic …


Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño Jun 2023

Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño

Health Sciences and Kinesiology Faculty Articles

Context

One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed …


Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari May 2023

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5ad displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5ad …


Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif Apr 2023

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H+ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …


Jak2/Stat5 Pathway Mutation Frequencies In South African Bcr/Abl Negative Mpn Patients, Shires K, Rust A, Harryparsad R, Coburn J, Gopie R Apr 2023

Jak2/Stat5 Pathway Mutation Frequencies In South African Bcr/Abl Negative Mpn Patients, Shires K, Rust A, Harryparsad R, Coburn J, Gopie R

Hematology/Oncology and Stem Cell Therapy

Background: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPNBCR/ABLneg), with JAK2V617F being found in 50-97% of MPNBCR/ABLneg subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPNBCR/ABLneg population may have a different mutational landscape. Objectives: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPNBCR/ABLneg population, thus determining the relevance of these molecular tests in this group. We also investigated the haematopathological relevance of each test request, to assess testing practises. Method: This study involved the retrospective audit of 886 patients for whom JAK2V617F mutation testing had …


Acquired Amegakaryocytic Thrombocytopenic Purpura: A Review Of Therapeutic Options, Syed Ather Hussain, Aneeqa Zafar, Hafsa Faisal, Mohammad Ammad Ud Din Apr 2023

Acquired Amegakaryocytic Thrombocytopenic Purpura: A Review Of Therapeutic Options, Syed Ather Hussain, Aneeqa Zafar, Hafsa Faisal, Mohammad Ammad Ud Din

Hematology/Oncology and Stem Cell Therapy

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by either a marked decrease or a complete absence of megakaryocytes with preservation of all other cell lines. More than 60 cases of AATP have been reported in literature thus far. Due to the rarity of this disease, no standard treatment guidelines have been established and therapy is based on a handful of case studies and expert opinion. Herein, we provide a comprehensive review on currently utilized therapeutic options for AATP.


Predicting If Lung Cancer Will Relapse—The Role Of Neutrophil/Lymphocyte Ratio, Abigail Chan, Søren Bentzen, Amit Rout, Kenneth Miller Jan 2023

Predicting If Lung Cancer Will Relapse—The Role Of Neutrophil/Lymphocyte Ratio, Abigail Chan, Søren Bentzen, Amit Rout, Kenneth Miller

Hematology/Oncology and Stem Cell Therapy

Objective/Background: Baseline neutrophil/lymphocyte ratio (NLR), a surrogate marker for systemic inflammation and immunosuppression, is a well-studied prognostic marker in nonsmall cell lung cancer (NSCLC). This study tests if interim NLR is prognostic in NSCLC patients in remission. Methods: This single-center, retrospective cohort study analyzed 131 NSCLC patients treated from 2010 to 2015 who achieved complete remission. NLR was calculated at baseline and from the first available blood sample during remission. Kaplan–Meier estimates of overall survival (OS) and time to recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox proportional hazards model. Results: Of …


Impact Of Pre-Transplant Induction Therapy On Outcomes Of Patients Who Undergo Autologous Stem Cell Transplantation For Mantle Cell Lymphoma In First Complete Remission, Omar Albanyan, Samer Alkassis, Seongho Kim, Andrew Kin, Asif Alavi, Lois Ayash, Voravit Ratanatharathorn, Dipenkumar Modi, Joseph P. Uberti, Abhinav Deol Jan 2023

Impact Of Pre-Transplant Induction Therapy On Outcomes Of Patients Who Undergo Autologous Stem Cell Transplantation For Mantle Cell Lymphoma In First Complete Remission, Omar Albanyan, Samer Alkassis, Seongho Kim, Andrew Kin, Asif Alavi, Lois Ayash, Voravit Ratanatharathorn, Dipenkumar Modi, Joseph P. Uberti, Abhinav Deol

Hematology/Oncology and Stem Cell Therapy

Mantle cell lymphoma is a rare subtype of non-Hodgkin’s lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical trials. We retrospectively evaluated 66 patients diagnosed with mantle cell lymphoma who achieved first complete response after induction chemotherapy followed by autologous stem cell transplant. Treatment groups were divided into lowintensity versus high-intensity regimens. Our data showed the intensity of induction regimen does not impact posttransplant outcomes of mantle cell lymphoma who underwent autologous stem cell transplant in first complete response.


Promising Effect Of Pdl1 Inhibitors In The Front-Line Management Of Primary Aggressive Central Nervous System Lymphoma: A Case Report, Rasha El-Tawab, Abdulaziz Hamada, Rehab Elhagracy, Karen Pinto, Salem Alshemmari Jan 2023

Promising Effect Of Pdl1 Inhibitors In The Front-Line Management Of Primary Aggressive Central Nervous System Lymphoma: A Case Report, Rasha El-Tawab, Abdulaziz Hamada, Rehab Elhagracy, Karen Pinto, Salem Alshemmari

Hematology/Oncology and Stem Cell Therapy

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma that involves the central nervous system. The standard treatment involves chemotherapy with high-dose methotrexate. To the best of our knowledge, this is the first reported case of employing checkpoint inhibitor, nivolumab, alone to treat a patient with PCNSL who could not tolerate the induction therapy. In aggressive cases of PCNSL where chemotherapy may become futile, stand-alone checkpoint inhibitors should be considered as the front-line treatment protocol.


Predictors And Management Of Relapse To Axicabtagene Ciloleucel In Patients With Aggressive B-Cell Lymphoma, Jose Vicente Forero-Forero, Paula A. Lengerke-Diaz, Eider Moreno-Cortes, Megan Melody, Zaid Abdel Rahman, Allison C. Rosenthal, Mohamed A. Kharfan-Dabaja, Januario E. Castro Jan 2023

Predictors And Management Of Relapse To Axicabtagene Ciloleucel In Patients With Aggressive B-Cell Lymphoma, Jose Vicente Forero-Forero, Paula A. Lengerke-Diaz, Eider Moreno-Cortes, Megan Melody, Zaid Abdel Rahman, Allison C. Rosenthal, Mohamed A. Kharfan-Dabaja, Januario E. Castro

Hematology/Oncology and Stem Cell Therapy

Objective/background: Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal. Methods: We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy. Results: Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. …


Immune Checkpoint Inhibitor-Induced Pneumonitis: Incidence, Clinical Characteristics, And Outcomes, Harsha Banavasi, Seongho Kim, Samer Alkassis, Asil Daoud, Amir Laktineh, Misako Nagasaka, Ammar Sukari, Ayman O. Soubani Jan 2023

Immune Checkpoint Inhibitor-Induced Pneumonitis: Incidence, Clinical Characteristics, And Outcomes, Harsha Banavasi, Seongho Kim, Samer Alkassis, Asil Daoud, Amir Laktineh, Misako Nagasaka, Ammar Sukari, Ayman O. Soubani

Hematology/Oncology and Stem Cell Therapy

Background: Immune checkpoint inhibitors (ICIs) are the newest class of anticancer drugs. Pneumonitis is increasingly being recognized as a potential complication of these agents. Methods: We conducted a retrospective study of patients who received ICIs at a comprehensive cancer center. We collected data on demographics, type of malignancy, type of ICI agent, incidence of pneumonitis up to 6 weeks after receiving ICI agent, clinical characteristics, and risk factors for overall survival in patients who develop pneumonitis. Results: A total of 654 patients received ICIs during the study period. The most common type of cancer for which ICI was given was …


Changes In Heme Levels During Acute Vaso-Occlusive Crisis In Sickle Cell Anemia, Evilazio Cunha Cardoso, Pedro Vieira Silva-Neto, Bidossessi Wilfried Hounkpe, Francine Chenou, Cintia Cristina Mateus Xerez Albuquerque, Nadja Pinto Garcia, Alexander Leonardo Silva-Junior, Adriana Malheiro, Purim Cesar, Franciele De Lima, Erich V. De Paula, Nelson Abrahim Fraiji Jan 2023

Changes In Heme Levels During Acute Vaso-Occlusive Crisis In Sickle Cell Anemia, Evilazio Cunha Cardoso, Pedro Vieira Silva-Neto, Bidossessi Wilfried Hounkpe, Francine Chenou, Cintia Cristina Mateus Xerez Albuquerque, Nadja Pinto Garcia, Alexander Leonardo Silva-Junior, Adriana Malheiro, Purim Cesar, Franciele De Lima, Erich V. De Paula, Nelson Abrahim Fraiji

Hematology/Oncology and Stem Cell Therapy

Objective/Background: Sickle cell anemia (SCA) is associated with increased levels of extracellular heme, which is a key mediator of inflammation in this condition. Despite abundant evidence supporting this concept in cell and animal models, few studies addressed the association between heme levels and the development and severity of acute vaso-occlusive crises (VOC) in humans. Methods: A cross-sectional study was conducted in patients with acute VOC. Total extracellular heme levels were measured in both plasma and serum at admission and after convalescence, and correlated with other clinical and laboratory markers of SCA severity. Results: A total of 28 episodes of VOC …